Evidence map›Paper›PMID 35071407›Full record

ArticleAnnals of translational medicine2021

Preclinical efficacy and safety evaluation of interleukin-6-knockdown CAR-T cells targeting at CD19.

Hairuo Wen, Guitao Huo, Tiantian Hou, Zhe Qu, Juanjuan Sun, Zhou Yu, Liqing Kang, Manhong Wang, Xiaoyan Lou, Lei Yu and 1 more

Abstract read
In one paragraph

Article in Annals of translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Article
  2. Review
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  6. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Hairuo Wen *Key Laboratory of Beijing for Safety Evaluation of Drugs, National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, Beijing, China.
Guitao Huo *Key Laboratory of Beijing for Safety Evaluation of Drugs, National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, Beijing, China.
Tiantian Hou *Key Laboratory of Beijing for Safety Evaluation of Drugs, National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, Beijing, China.
Zhe QuKey Laboratory of Beijing for Safety Evaluation of Drugs, National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, Beijing, China.
Juanjuan SunShanghai Unicar Biomed-Pharmaceutical Technology Co. Ltd., Shanghai, China.
Zhou YuShanghai Unicar Biomed-Pharmaceutical Technology Co. Ltd., Shanghai, China.
Liqing KangShanghai Unicar Biomed-Pharmaceutical Technology Co. Ltd., Shanghai, China.
Manhong WangKey Laboratory of Beijing for Safety Evaluation of Drugs, National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, Beijing, China.
Xiaoyan LouShanghai Unicar Biomed-Pharmaceutical Technology Co. Ltd., Shanghai, China.
Lei YuShanghai Unicar Biomed-Pharmaceutical Technology Co. Ltd., Shanghai, China.
Yan HuoKey Laboratory of Beijing for Safety Evaluation of Drugs, National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, Beijing, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundssCART-19 cells with

methodsNSG mice were administered Raji-Luc and then singly dosed with ssCART-19 cells via intravenous infusion. ssCART-19 DNA fragments were quantified in different tissues by qPCR, and the optical intensity of Raji-Luc was determined for evaluate the efficacy of regular CAR-T and ssCART-19 cells. In toxicity study, clinical symptoms observation, body weight measurements, serum biochemical analysis, human cytokine detection, lymphocytes subsets quantification, necropsy and histopathological examination were performed.

resultsThe ssCART-19 DNA was mainly concentrated in the liver within 3 hours, and was widely distributed in most of the organs/tissues for 4 weeks after administration. Chimeric antigen receptor gene modified T cells (CAR-Ts) were detected in the peripheral blood with a significant increase in number beginning at approximately 3 weeks. ssCART-19 administration resulted in increased of interferon-gamma (IFN-γ), tumor necrosis factor (TNF), interleukin-2 (IL-2), and IL-17A and decreased IL-10 and IL-6 levels. ssCART-19 inhibited the proliferation of Raji-Luc cells in tumor-bearing NSG mice, and reduced the incidence of lymphomas in the liver, kidneys and spleen. It alleviated clinical symptoms caused by tumor cell proliferation in treated animals.

conclusionsssCART-19 prolongs the survival time of tumor-bearing mice without obvious risks of immunotoxicity and tumorigenicity. ssCART-19 DNA was found in the brains of treated animals, however no significant central nervous system toxicity was observed. These data were used to support an investigational new drug (IND) application of ssCART-19 for clinical trial in China.

Indexed as

biodistributionChimeric antigen receptor T cellcytokine release syndrome (CRS)IL-6 knockdowntoxicity

Identifiers

PMID35071407
PMCPMC8743728

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.